Kun Huang

In this paper, we investigate the problem of network backbone discovery. In complex systems, a "backbone" takes a central role in carrying out the system functionality and carries the bulk of system traffic. It also both simplifies and highlight underlying networking structure. Here, we propose an integrated graph theoretical and information theoretical network backbone model. We develop an efficient mining algorithm based on Kullback-Leibler divergence optimization procedure and maximal weight connected subgraph discovery procedure. A detailed experimental evaluation demonstrates both the effectiveness and efficiency of our approach. The case studies in the real world domain further illustrates the usefulness of the discovered network backbones.

Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. We aimed to identify biomarkers associated with NIS expression such that mechanisms underlying NIS modulation in human breast tumors may be elucidated.

Temporal causal modeling can be used to recover the causal structure among a group of relevant time series variables. Several methods have been developed to explicitly construct temporal causal graphical models. However, how to best understand and conceptualize these complicated causal relationships is still an open problem. In this paper, we propose a decomposition approach to simplify the temporal graphical model. Our method clusters time series variables into groups such that strong interactions appear among the variables within each group and weak (or no) interactions exist for cross-group variable pairs. Specifically, we formulate the clustering problem for temporal graphical models as a regression-coefficient sparsification problem and define an interesting objective function which balances the model prediction power and its cluster structure. We introduce an iterative optimization approach utilizing the Quasi-Newton method and generalized ridge regression to minimize the objective function and to produce a clustered temporal graphical model. We also present a novel optimization procedure utilizing a graph theoretical tool based on the maximum weight independent set problem to speed up the Quasi-Newton method for a large number of variables. Finally, our detailed experimental study on both synthetic and real datasets demonstrates the effectiveness of our methods.

Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal^K mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/ Contact:taslim.2@osu.edu; khuang@bmi.osu.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Dimensional reduction of high dimensional data can be achieved by keeping only the relevant eigenmodes after principal component analysis. However, differentiating relevant eigenmodes from the random noise eigenmodes is problematic. A new method based on the random matrix theory and a statistical goodness-of-fit test is proposed in this paper. It is validated by numerical simulations and applied to real-time magnetic resonance cardiac cine images.

Microscopic imaging is an important tool for characterizing tissue morphology and pathology. 3D reconstruction and visualization of large sample tissue structure requires registration of large sets of high-resolution images. However, the scale of this problem presents a challenge for automatic registration methods. In this paper we present a novel method for efficient automatic registration using graphics processing units (GPUs) and parallel programming. Comparing a C++ CPU implementation with Compute Unified Device Architecture (CUDA) libraries and pthreads running on GPU we achieve a speed-up factor of up to 4.11× with a single GPU and 6.68× with a GPU pair. We present execution times for a benchmark composed of two sets of large-scale images: mouse placenta (16K ×16K pixels) and breast cancer tumors (23K ×62K pixels). It takes more than 12 hours for the genetic case in C++ to register a typical sample composed of 500 consecutive slides, which was reduced to less than 2 hours using two GPUs, in addition to a very promising scalability for extending those gains easily on a large number of GPUs in a distributed system.

Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types.